Intravenous immunoglobulin (IVIG) is a blood product administered intravenously. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. It contains the pooled IgG immunoglobulins (antibodies extracted from the plasma of over a thousand blood donors). Immunoglobulin G ( IgG) is a Monomeric Immunoglobulin, built of two heavy chains γ and two light chains. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended IVIG's effects last between 2 weeks and 3 months. It is mainly used as treatment in three major categories:

• Immune deficiencies - Immune deficiencies such as X-linked agammaglobulinemia, hypogammaglobulinemia (primary immune deficiencies), and acquired compromised immunity conditions ([secondary immune deficiencies), featuring low antibody levels. In Medicine, immunodeficiency (or immune deficiency) is a state in which the Immune system 's ability to fight Infectious disease is compromised X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia XLA, Bruton type agammaglobulinemia) is a rare X-linked genetic disorder Hypogammaglobulinemia is a type of Immune disorder characterized by a reduction in all types of Gamma globulins It is distinguished from Dysgammaglobulinemia Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily
• Inflammatory and autoimmune diseases. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues
• Acute infections.

Contents 1 Mechanism of action 2 IVIG notes 3 Uses of IVIG 3.1 FDA-approved indications 3.2 Off-label Uses 4 Complications and side effects 5 References

Mechanism of action

IVIG is given as a plasma protein replacement therapy (IgG) for immune deficient patients which have decreased or abolished antibody production capabilities. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily In these immune deficient patients, IVIG is administered to maintain adequate antibodies levels to prevent infections and confers a passive immunity. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily An infection is the detrimental Colonization of a host Organism by a foreign Species. Treatment is given every 3-4 weeks. In the case of patients with autoimmune disease, IVIG is administered at a high dose (generally 1-2 grams IVIG per kg body weight) to attempt to decrease the severity of the autoimmune disease.

The precise mechanism by which IVIG suppresses harmful inflammation has not been definitively established but is believed to involve the inhibitory Fc receptor. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens An Fc receptor is a protein found on the surface of certain cells - including Natural killer cells Macrophages Neutrophils and Mast cells - that ^[1][2] The actual primary target(s) of IVIG in autoimmune disease are still unclear, however. IVIG may work via a multi-step model where the injected IVIG first forms a type of immune complex in the patient. ^[3] Once these immune complexes are formed, they interact with activating Fc receptors on dendritic cells^[4]which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state.

Additionally, the donor antibody may bind directly with the abnormal host antibody, stimulating its removal. Alternatively, the massive quantity of antibody may stimulate the host's complement system, leading to enhanced removal of all antibodies, including the harmful ones. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily The complement system is a Biochemical cascade that helps clear Pathogens from an organism IVIG also blocks the antibody receptors on immune cells (macrophages), leading to decreased damage by these cells, or regulation of macrophage phagocytosis. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole

IVIG may also regulate the immune response by reacting with a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by Monocyte is a type of Leukocyte, part of the Human body 's Immune system. ^[5]

A recent report stated that IVIG application to activated T cells leads to their decreased ability to engage microglia. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Microglia are a type of Glial cell that acts as the first and main form of active immune defense in the Central nervous system (CNS As a result of IVIG treatment of T cells, the findings showed reduced levels of tumor necrosis factor-alpha and interleukin-10 in T cell-microglia co-culture. Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic Interleukin -10 (IL-10 or IL10 also known as human cytokine synthesis inhibitory factor (CSIF is an anti- Inflammatory Cytokine. The results add to the understanding of how IVIG may affect inflammation of the central nervous system in autoimmune inflammatory diseases. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues ^[6]

IVIG is useful in some acute infection cases such as in Kawasaki's Disease and pediatric HIV infection. Kawasaki disease Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome

IVIG notes

• IVIG is an infusion of IgG antibodies only. Immunoglobulin G ( IgG) is a Monomeric Immunoglobulin, built of two heavy chains γ and two light chains. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Therefore, peripheral tissues that are defended mainly by IgA antibodies, such as the eyes, lungs, gut and urinary tract are not fully protected by the IVIG treatment. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity Eyes are organs that detect Light, and send signals along the Optic nerve to the visual areas of the brain lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive The urinary system (also called Excretory system or the genitourinary system (GUS is the Organ system that produces stores and eliminates Urine.
• XLA patients are immune to the most virulent adverse effect, anaphylactic shock, as they do not have the antibodies to react against the treatment. X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia XLA, Bruton type agammaglobulinemia) is a rare X-linked genetic disorder Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals Anaphylactic shock has a higher chance to occur in IgA deficient patients which do have other antibody types. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity
• In case of recurring side effects, it is recommended to slow the pace of the IVIG administration and to reduce the dosage. It is also advisable to change IVIG brand, as some people react against to a specific brand.
• If the patient is diabetic, he should take into consideration the medium in which the antibodies are solubilized in the IVIG treatment, as some brand solubilize antibodies with high concentrated sugars (such as sucrose and maltose). Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Sugar is a class of edible Crystalline substances mainly Sucrose, Lactose, and Fructose. Solubility of Pure SucroseTemperature(Cg Maltose, or malt sugar is a Disaccharide formed from two units of Glucose joined with an α(1→4 linkage
• FDA guidelines for IVIG state the product should be:
  • Prepared out of at least 1,000 different human donors.
  • All four IgG subgroups (1-4) should be present.
  • The IgG should maintain biological activity and lifetime of at least 21 days.
  • Does not contain samples which are HIV, hepatitis B, hepatitis C positive. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Hepatitis C is a blood-borne infectious disease that is caused by the Hepatitis C virus ( HCV) affecting the Liver.
  • Screened and treated in a manner that destroys viruses. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable
• IVIG is also considered a modulator of the immune system and was shown to be beneficial in treating numerous autoimmune diseases such as relapsing and remitting multiple sclerosis (MS), myasthenia gravis, pemphigus, polymyositis (PM), dermatomyositis (DM), Wegener's granulomatosis (WG), Churg-Strauss syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) and more. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Myasthenia gravis (literally "serious muscle-weakness" from Greek μύς "muscle" "weakness" and Latin gravis Pemphigus (from the Greek pemphix: bubble or blister is an Autoimmune disease of the Skin and mucous membranes that causes vesicles Polymyositis is a type of Inflammatory myopathy, related to Dermatomyositis and Inclusion body myositis. Dermatomyositis (DM is a connective-tissue disease related to Polymyositis (PM that is characterized by Inflammation of the muscles and the skin Wegener's granulomatosis is a form of Vasculitis that affects the Lungs Kidneys and other organs Churg-Strauss syndrome (also known as allergic Granulomatosis) is a medium and small vessel autoimmune Vasculitis, leading to Necrosis Chronic Inflammatory Demyelinating Polyneuropathy (CIDP is an acquired immune-mediated inflammatory disorder of the Peripheral nervous system but often can have
• IVIG can be given to pregnant women.
• IVIG is also used as a treatment for unexplained recurring miscarriages. The effectiveness of the therapy is controversial.

Uses of IVIG

Dosage of IVIG is dependent on indication.

For primary immune dysfunction 100 to 400 mg/kg of body weight every 3 to 4 weeks is implemented.

For neurological and autoimmune diseases 2 grams per kilogram of body weight is implemented for three to six months over a five day course once a month. Then maintenance therapy of 100 to 400 mg/kg of body weight every 3 to 4 weeks follows.

FDA-approved indications

• Allogeneic bone marrow transplant
• Chronic lymphocytic leukemia
• Idiopathic thrombocytopenic purpura
• Pediatric HIV
• Primary immunodeficiencies
• Kawasaki disease
• Kidney transplant with a high antibody recipient or with an ABO incompatible donor

In 2004 the FDA approved the Cedars-Sinai IVIG Protocol which has been 90-95% successful in removing antibodies from the blood of kidney transplant recipients so that they can accept a living donor kidney from any healthy donor no matter blood type (ABO incompatible) or tissue match. Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL" is a type of Leukemia, or cancer of the white blood cells ( Lymphocytes Idiopathic thrombocytopenic purpura (ITP is the condition of having a low Platelet count ( Thrombocytopenia) of no known cause ( Idiopathic) Kawasaki disease Kidney transplantation or renal transplantation is the Organ transplant of a Kidney in a patient with End-stage renal disease.

Off-label Uses

• Chronic fatigue syndrome
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Clostridium difficile colitis
• Dermatomyositis and polymyositis
• Graves' ophthalmopathy
• Guillain-Barré syndrome
• Kawasaki disease
• Muscular Dystrophy
• Inclusion body myositis
• Lambert-Eaton syndrome
• Lupus erythematosus
• Multifocal motor neuropathy
• Multiple sclerosis
• Myasthenia gravis
• Neonatal alloimmune thrombocytopenia
• Parvovirus B19
• Pemphigus
• Post-transfusion purpura
• Renal transplant rejection
• Spontaneous Abortion/Miscarriage
• Stiff person syndrome
• Severe sepsis and septic shock in critically ill adults^[7]
• Toxic epidermal necrolysis
• In chronic lymphocytic leukemia and multiple myeloma, as well as various rare deficiencies of immunoglobulin synthesis (e. Chronic fatigue syndrome ( CFS) is the most common name given to a poorly understood variably debilitating disorder or disorders of uncertain causation Chronic Inflammatory Demyelinating Polyneuropathy (CIDP is an acquired immune-mediated inflammatory disorder of the Peripheral nervous system but often can have Clostridium difficile (pronounced /klɒsˈtrɪdiəm dɪˈfɪsɪli/ also known as CDF/cdf' or 'C Dermatomyositis (DM is a connective-tissue disease related to Polymyositis (PM that is characterized by Inflammation of the muscles and the skin Polymyositis is a type of Inflammatory myopathy, related to Dermatomyositis and Inclusion body myositis. Graves' disease is a Thyroid disorder characterized by goiter, Exophthalmos, "orange-peel" skin and Hyperthyroidism. Guillain-Barré syndrome ( GBS) (in French ɡilɛ̃ baˈʁe in English ˈɡiːlæn ˈbɑreɪ /ɡiːˈæn bəˈreɪ/ etc Kawasaki disease Muscular dystrophy (MD refers to a group of genetic, Hereditary Muscle diseases that cause progressive muscle weakness Sporadic inclusion body myositis ( sIBM) is an inflammatory Muscle Disease, characterized by slowly progressive weakness and wasting of the Lambert-Eaton myasthenic syndrome (LEMS is a rare Autoimmune disorder which affects calcium channels of the nerve-muscle ( neuromuscular) junction Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Myasthenia gravis (literally "serious muscle-weakness" from Greek μύς "muscle" "weakness" and Latin gravis Neonatal Alloimmune Thrombocytopenia ( NAITP or NAIT or NAT for short or feto-maternal alloimmune thrombocytopenia, FMAITP Pemphigus (from the Greek pemphix: bubble or blister is an Autoimmune disease of the Skin and mucous membranes that causes vesicles Stiff person syndrome (SPS (or stiff-man syndrome outside the USA is a rare neurologic disorder of unknown Etiology. Septic shock is a very serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of Infection and Sepsis, though the Toxic epidermal necrolysis (TEN also known as Lyell's syndrome, is a life-threatening dermatological condition that is frequently induced by a reaction to medications Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL" is a type of Leukemia, or cancer of the white blood cells ( Lymphocytes Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a type of g. X-linked agammaglobulinemia, hypogammaglobulinemia), IVIG is administered to maintain adequate immunoglobulin levels to prevent infections. X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia XLA, Bruton type agammaglobulinemia) is a rare X-linked genetic disorder Hypogammaglobulinemia is a type of Immune disorder characterized by a reduction in all types of Gamma globulins It is distinguished from Dysgammaglobulinemia An infection is the detrimental Colonization of a host Organism by a foreign Species.
• Common Variable Immune Deficiency

Complications and side effects

Complications of IVIG therapy include

• headache
• dermatitis - usually peeling of the skin of the palms and soles
• infection (such as HIV or viral hepatitis) by contaminated blood product; there is also an as yet unknown risk of contracting variant CJD (vCJD). A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted Dermatitis is a Blanket term meaning any " Inflammation of the skin" (e Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately
• pulmonary edema from fluid overload, due to the high colloid oncotic pressure of IVIG
• allergic/anaphylactic reactions
• damage such as hepatitis caused directly by antibodies contained in the pooled IVIG
• acute renal failure
• venous thrombosis
• aseptic meningitis

References

5. Noah S Scheinfeld. Intravenous Immunoglobulin. Emedicine. http://www.emedicine.com/med/topic3546.htm

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